The Effect Of Coagulation On The Pathway Of Coagulation

Hemophilia A is a known X-linked recessive disorder. This condition or bleeding disorder is characterized by a deficiency in the activity of a coagulation factor, which in this case is F8 or coagulation factor VIII. This condition is clinically known to be heterogeneous and its severity depends on the plasma level of the coagulation factor VIII. Varying levels of hemophilia exist which are categorized based on percentage of coagulation factor within blood plasma compared to normal levels.

Lab values during DIC are also of great importance. There is no specific test for DIC but a combination of PT (prothrombin time), aPTT (activated partial thromboplastin time), fibrinogen, platelet count and d-dimmer are used to assist in the diagnosis of DIC (Cunningham, 1999). Since many disorders can cause an increase of each of these lab values, it is important to use the whole picture to make the diagnosis.

The gold standard method for Hemophilia A is DNA sequencing. It will detect the mutation in the affected male and the female carrier. In using direct sequencing, analyze a single nucleotide polymorphism to track the defective X-chromosome in the family. In addition, scientists can detect the essential regions of factor VIII, such as the promoter region, and all the exons and intron/exon boundaries. This method is cost effective and provides sufficient results (Keeney, Mitchell, & Goodeve 2010).

Factor V Leiden is the most common inherited form of thrombophilia (Stammers, Dorion, Trowbridge, Yen, Klayman, Murdock & Gilbert, 2005). Between 3 and 8 percent of people with European ancestry carry one copy of the factor V Leiden mutation in each cell, and about 1 in 5,000 people have two copies of the mutation (Stammers, Dorion, Trowbridge, Yen, Klayman, Murdock & Gilbert, 2005). People who inherit two copies of the mutation, one from each parent, have a higher risk of developing a clot than people who inherit one copy of the mutation. Considering that about 1 in 1,000 people per year in the general population will develop an abnormal blood clot, the presence of one copy of the factor V Leiden mutation increases that risk to 3 to 8 in 1,000, and having two copies of the mutation may raise the risk to as high as 80 in 1,000 (Stammers, Dorion, Trowbridge, Yen, Klayman, Murdock & Gilbert, 2005). Although, only about 10 percent of individuals with the factor V Leiden mutation ever develop

This organ system has a number of functions namely, to keep a constant body temperature as well as to ensure coagulation occurs specifically at the site of injury, as well as to ensure no added blood loss occurs to cause life-threatening effects. This process of blood coagulation is explained in three interconnected phases. In the first phase, the enzyme thrombokinase is activated due to the damage of tissue and the breaking down of platelets. Prothrombin is converted into thrombin by the disintegration of the thrombocytes, electrically charged calcium ions and other coagulation factors, as well as the blood activator and tissue activator which become involved in the coagulation process. The second phase includes production of the thrombin that transforms fibrinogen in the blood plasma into fibrin. The thrombus (or blood clotting) is formed by a fibrilliform mesh that encloses the blood cells. Lastly, the third phase, which takes place as retraction occurs of the fibres of the fibrin mesh. Solidification of the fibrous mesh takes place which closes the defect in the vascular wall. Coagulation is then followed by fibrinolysis (re-dissolution of the clot).

Rotational Thromboelastometry (ROTEM, TEM Innovations GmbH, Munich, Germany) and thromboelastography (TEG, Haemoscope, Braintree, MA) are whole blood coagulation analyzers that measure viscoelastic changes of the entire clotting process. Compared to the prothrombin time (PT/INR) and partial thromboplastin time (aPTT), which measure coagulation factor function, TEG/ROTEM can evaluate platelet function, clot strength, and fibrinolysis, (de Laz, Nascimento, & Rizoli, 2013). This additional information can help guide resuscitation efforts by classifying bleeding due to coagulopathy. As a result, the need for platelets, cryoprecipitate (fibrinogen, Factor VIII, von Willebrand factor, &

A coagulation profile work-up was done. His factor VIII activity concentration was found to be 260% of normal (normal: 60-150). Analyses for prothrombin O20210A

Essential Thrombocythemia occurs due to a mutation in Janus Kinase 2 (JAK2), THPO, MPL, TET2, and CALR genes. Mutations in JAK and CALR are most common in ET. JAK2 gene involved in blood cell proliferation by giving an instruction to form a protein that promotes the proliferation and growth of blood cells. This protein plays important role in JAK/STAT signaling pathway, which passes on chemical signals from outside the cell to the nucleus. When JAK2 is abnormally activated, it causes an overproduction of megakaryocyte, which resulted in an increase in platelets number in the peripheral blood. The elevation in the platelets number can cause thrombosis. The mutation in JAK2 replaces the valine (amino acid) with phenylalanine at position 617 in the protein (Tefferi, 2010).

Hemophilia is the name of a group of hereditary blood disorders that doesn’t allow the blood to clot normally (Frey 2009). More specifically hemophilia A, also known as factor VIII, is caused by a missing clotting protein coagulation factor VIII. It is often times referred to as the “Royal Disease” because of how it ran rampant through the royal families of England, Spain , Germany, and other European countries during the 19th and 20th century. Hemophilia A is inherited in X-linked recessive pattern. In males (who have only one X chromosome), one copy of the affected gene is enough to cause the condition. In females (who have two X chromosomes), a mutation on both of the genes would have to be present to cause the disorder. Because it is very unlikely that a female would have both altered copies on both of the genes females generally don’t get hemophilia. Since fathers can only pass on the Y chromosomes to their sons they can’t pass X-linked traits along (Hemophilia 2015). Hemophilia is linked to the mutation of the F8, on the X chromosome, as seen in Figure 1. Mutations in the F8 gene can cause faulty versions of the coagulation protein, therefore this protein cannot participate in the clotting process (Gersten 2014).

thrombocytopenia or abnormal platelet function. The time required to form a clot and for edges

Factor V, Leiden Thrombophilia, is an inherited blood clotting disorder. This is a mutation in the Factor V protein that causes blood clots. It is a very common genetic disorder. The reason for being named Factor V is because of the mutation it causes. Thrombophilia is an increased tendency to form abnormal blood clots that block the blood vessels. This genetic disorder has a lot of symptoms that can affect one's daily life. The treatment provided for this disorder is to eliminate the pain it causes because there is no cure for Factor V. The patient's care and medical intervention can influence the patient's outcome.

Hemophilia, also spelled haemophilia, it is a genetic disease, patient lack of coagulation factors inborn, so the function of blood coagulation is impedimental, also it is not easy to stop the bleeding. Normal blood clotting is made of blood platelet and a part of plasma protein. The function that related to plasma protein of coagulation is coagulation factors. The patient’s blood coagulation factors is less than normal people. When the blood vessel burst, blood is not easy to curdle, so it is difficult to stop the bleeding. Since the patient lack of some coagulation factors, When the blood vessel burst, it’s more difficult to coagulate than normal people, so they will lose more blood.

Thromboelastography also known as TEG is a serum laboratory test that determines coagulation of blood. Blood clotting is called hemostasis and is an active, extremely complex process, involving many interacting factors including clotting, fibrinolytic proteins, activators, inhibitors and cellular elements (Eitel, 2012). It can help in determining if a patient may have a clotting factor or anemia by looking at clot strength and fibrinolysis. The test is usually utilized for surgery and anesthesia and does not replace other serum coagulation tests such as prothrombin time (PT,INR) or partial thromboplastin time (aPTT). TEG is able to assess platelet function, clot strength, and fibrinolysis where these other tests cannot.

Hemophilia A is a disorder in which the blood doesn’t clot normally due to the lack of blood clothing factor VIII. Hemophilia A is also known as the ‘Classic Hemophilia.’ According to the CDC, hemophilia will occur in approximately 1 in 5,000 live births. It is called classic hemophilia due to the fact that this hemophilia is four times more common as hemophilia B. This disorder is mainly a hereditary bleeding disorder which is caused by an inherited X linked recessive trait. Some acquired forms do exist as well, largely in older patients, due to autoantibodies directed against factor VIII. The defected gene is located on the X chromosome. And it results from a heterogeneous mutation in factor VIII gene that maps for Xq28.

Coagulation is a process where there is a blood clot formation at the site of an injured blood vessel. Once there has been an injury to the blood vessel wall, vasoconstriction immediately occurs, and then we get primary haemostasis. Platelet activation occurs in this process and they adhere to the subendothelial complex. There is a formation of fibrin in this process and this leads to a haemostatic plug being formed at the site of injury. Secondary haemostasis also occurs simultaneously with primary haemostasis. In this process, tissue factors are involved in the initiation of the coagulation cascade. The end result of the coagulation cascade is the activation of thrombin. Thrombin is an important enzyme in haemostasis as it is needed for the conversion of fibrinogen to an insoluble fibrin monomer to form the matrix of the clot and also it is important for further platelet activation. (Khan and Dickerman, 2006; Hoffman, 2003; Clemetson, 2012; Arnout et al., 2006; Hawiger, 1987; Green, 2006)